Table_1_Piecing it together: atrophy profiles of hippocampal subfields relate to cognitive impairment along the Alzheimer’s disease spectrum.DOCX

IntroductionPeople with Alzheimer’s disease (AD) experience more rapid declines in their ability to form hippocampal-dependent memories than cognitively normal healthy adults. Degeneration of the whole hippocampal formation has previously been found to covary with declines in learning and memory, but the associations between subfield-specific hippocampal neurodegeneration and cognitive impairments are not well characterized in AD. To improve prognostic procedures, it is critical to establish in which hippocampal subfields atrophy relates to domain-specific cognitive declines among people along the AD spectrum. In this study, we examine high-resolution structural magnetic resonance imaging (MRI) of the medial temporal lobe and extensive neuropsychological data from 29 amyloid-positive people on the AD spectrum and 17 demographically-matched amyloid-negative healthy controls.MethodsParticipants completed a battery of neuropsychological exams including select tests of immediate recollection, delayed recollection, and general cognitive status (i.e., performance on the Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]). Hippocampal subfield volumes (CA1, CA2, CA3, dentate gyrus, and subiculum) were measured using a dedicated MRI slab sequence targeting the medial temporal lobe and used to compute distance metrics to quantify AD spectrum-specific atrophic patterns and their impact on cognitive outcomes.ResultsOur results replicate prior studies showing that CA1, dentate gyrus, and subiculum hippocampal subfield volumes were significantly reduced in AD spectrum participants compared to amyloid-negative controls, whereas CA2 and CA3 did not exhibit such patterns of atrophy. Moreover, degeneration of the subiculum along the AD spectrum was linked to a significant decline in general cognitive status measured by the MMSE, while degeneration scores of the CA1 and dentate gyrus were more widely associated with declines on the MMSE and tests of learning and memory.DiscussionThese findings provide evidence that subfield-specific patterns of hippocampal degeneration, in combination with cognitive assessments, may constitute a sensitive prognostic approach and could be used to better track disease trajectories among individuals on the AD spectrum.

引言阿尔茨海默病患者（AD）相较于认知正常的健康成年人，其海马依赖性记忆形成能力衰退更为迅速。既往研究表明，整个海马结构的退化与学习和记忆能力的下降相关联，但AD中特定亚字段海马神经退化的认知障碍关联尚不明确。为了改善预后程序，确立在海马亚字段萎缩与AD谱系人群特定认知衰退之间的关联至关重要。在本研究中，我们分析了29名淀粉样蛋白阳性的AD谱系受试者和17名人口统计学上匹配的淀粉样蛋白阴性健康对照者的内侧颞叶高分辨率结构磁共振成像（MRI）和广泛的神经心理学数据。方法受试者完成了一系列神经心理学测试，包括即刻回忆、延迟回忆和一般认知状态测试（即Mini-Mental State Examination [MMSE]和Montreal Cognitive Assessment [MoCA]的表现）。使用专门针对内侧颞叶的MRI切片序列测量海马亚字段体积（CA1、CA2、CA3、齿状回和穹窿），并计算距离指标以量化AD谱系特异性萎缩模式和其对认知结果的影响。结果我们的结果与先前研究一致，表明与淀粉样蛋白阴性对照组相比，AD谱系受试者的CA1、齿状回和穹窿海马亚字段体积显著减小，而CA2和CA3未表现出这种萎缩模式。此外，AD谱系中穹窿的退化与通过MMSE测量的总体认知状态显著下降相关，而CA1和齿状回的退化评分与MMSE和学习记忆测试的下降更为广泛相关。讨论这些发现提供了证据，表明海马特定亚字段退化模式与认知评估相结合可能构成一种敏感的预后方法，并可用于更好地追踪AD谱系个体的疾病轨迹。